chr11-74013419-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_001286577.2(C2CD3):c.7028G>A(p.Arg2343Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000925 in 1,307,684 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2343W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000086 ( 1 hom. )

Consequence

C2CD3
NM_001286577.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.45

Publications

1 publications found

Variant links:

Genes affected

C2CD3 (HGNC:24564): (C2 domain containing 3 centriole elongation regulator) This gene encodes a protein that functions as a regulator of centriole elongation. Studies of the orthologous mouse protein show that it promotes centriolar distal appendage assembly and is also required for the recruitment of other ciliogenic proteins, including intraflagellar transport proteins. Mutations in this gene cause orofaciodigital syndrome XIV (OFD14), a ciliopathy resulting in malformations of the oral cavity, face and digits. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Nov 2014]

C2CD3 Gene-Disease associations (from GenCC):

orofaciodigital syndrome type 14
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet

C2CD3 links:

ENSG00000298570 (HGNC:):

ENSG00000298570 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02752325).

BP6

Variant 11-74013419-C-T is Benign according to our data. Variant chr11-74013419-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1558546.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000145 (22/152244) while in subpopulation EAS AF = 0.00368 (19/5168). AF 95% confidence interval is 0.00241. There are 0 homozygotes in GnomAd4. There are 12 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286577.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD3	NM_001286577.2	MANE Select	c.7028G>A	p.Arg2343Gln	missense	Exon 33 of 33	NP_001273506.1	Q4AC94-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C2CD3	ENST00000334126.12	TSL:5 MANE Select	c.7028G>A	p.Arg2343Gln	missense	Exon 33 of 33	ENSP00000334379.7	Q4AC94-5
C2CD3	ENST00000681143.1		c.6623G>A	p.Arg2208Gln	missense	Exon 30 of 30	ENSP00000505970.1	A0A7P0Z4H1
C2CD3	ENST00000923534.1		c.6533G>A	p.Arg2178Gln	missense	Exon 32 of 32	ENSP00000593593.1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00367

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000184

AC:

AN:

48998

AF XY:

0.000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00315

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000675

GnomAD4 exome

AF:

0.0000857

AC:

AN:

1155440

Hom.:

Cov.:

AF XY:

0.0000789

AC XY:

AN XY:

570364

show subpopulations

African (AFR)

AF:

0.0000416

AC:

AN:

24028

American (AMR)

AF:

0.00

AC:

AN:

16160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19242

East Asian (EAS)

AF:

0.00243

AC:

AN:

28856

South Asian (SAS)

AF:

0.000231

AC:

AN:

56272

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5012

European-Non Finnish (NFE)

AF:

0.00000647

AC:

AN:

926764

Other (OTH)

AF:

0.000186

AC:

AN:

48516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000145

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41550

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00368

AC:

AN:

5168

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.0000538

AC:

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.034

Eigen

Benign

0.15

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.48

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

1.5

PROVEAN

Benign

-0.99

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.021

Vest4

0.61

MVP

0.21

ClinPred

0.19

GERP RS

3.4

Varity_R

0.31

gMVP

0.35

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over